Bayesian network meta-analysis of first-line immunotherapy versus TKI for advanced hepatocellular carcinoma

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Frontiers in Medicine Published May 14, 2026 Medically reviewed May 14, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider that first-line immunotherapy may improve survival in advanced hepatocellular carcinoma without significantly increasing severe toxicity.

This is a Bayesian network meta-analysis that synthesized evidence from randomized controlled trials for first-line treatment of advanced hepatocellular carcinoma. The scope included 14 regimens, such as sintilimab, bevacizumab, and nivolumab, versus tyrosine kinase inhibitor monotherapy in 7,301 patients with HBV, HCV, or non-viral etiologies.

The authors found that immunotherapy-based regimens significantly improved overall survival compared to TKI monotherapy, with a pooled hazard ratio of 0.79 (95% CI 0.74-0.84). Progression-free survival was also significantly improved, with a hazard ratio of 0.70 (95% CI 0.58-0.85). The objective response rate was increased, with an odds ratio of 3.20 (95% CI 2.49-4.12).

In subgroup analyses, overall survival was significantly improved in HBV-positive patients (HR 0.73, 95% CI 0.67-0.79) and HCV-positive patients (HR 0.82, 95% CI 0.72-0.93). Progression-free survival was not statistically significant in NBNC patients (HR 0.74, 95% CI 0.52-1.06). The sintilimab-bevacizumab combination showed the greatest OS improvement versus sorafenib (HR 0.57, 95% CI 0.43-0.75).

Grade 3 or higher treatment-related adverse events were not significantly increased versus TKI monotherapy (OR 1.16, 95% CI 0.75-1.80). Tislelizumab and nivolumab were associated with lower risks of severe toxicity. The authors note that follow-up duration was not reported and the analysis is limited to the evaluated regimens and populations.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedMay 2026

View Original Abstract ↓

BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized the front-line treatment of advanced hepatocellular carcinoma (HCC). However, the comparative efficacy and safety of different ICI-based regimens—and their consistency across etiologic subgroups [HBV, HCV, and non-HBV/non-HCV (NBNC)]—remain uncertain. This study conducted a Bayesian network meta-analysis (NMA) of recent randomized controlled trials (RCTs) to compare the first-line immunotherapy strategies both overall and by viral etiology.MethodsA systematic search of PubMed, Embase, the Cochrane Library, and Web of Science was conducted from inception through August 1, 2025. Prespecified primary outcomes were overall survival (OS) and progression-free survival (PFS); secondary outcomes included objective response rate (ORR) and grade ≥3 treatment-related adverse events (TRAEs). Hazard ratios (HRs) and odds ratios (ORs) were pooled in a Bayesian NMA contrasting ICI-based regimens with tyrosine kinase inhibitor (TKI) monotherapy in the overall advanced HCC population and in HBV, HCV, and NBNC strata. Protocol registration: PROSPERO CRD420251131167.ResultsTen RCTs (n=7,301) evaluating 14 first-line regimens were included. Compared to TKI monotherapy, immunotherapy significantly improved OS (HR = 0.79, 95% CI 0.74-0.84) and PFS (HR = 0.70, 95% CI 0.58-0.85), increased ORR (OR = 3.20, 95% CI 2.49-4.12), and did not significantly increase grade ≥3 TRAEs (OR = 1.16, 95% CI 0.75-1.80). Benefits were more pronounced in HBV-positive patients (OS: HR = 0.73, 95% CI 0.67-0.79; PFS: HR = 0.54, 95% CI 0.48-0.61). HCV-positive patients also derived an OS benefit (HR = 0.82, 95% CI 0.72-0.93), whereas PFS improvement in NBNC patients was not statistically significant (HR = 0.74, 95% CI 0.52-1.06). In the NMA, sintilimab plus a bevacizumab biosimilar (Sinti-Bev) showed the greatest OS improvement versus sorafenib (HR = 0.57, 95% CI 0.43-0.75), followed by camrelizumab plus rivoceranib (Camre-Rivo; HR = 0.62, 95% CI 0.49-0.80). For PFS, anlotinib plus penpulimab (Anlo-Penpu) and Camre-Rivo ranked the highest (both HR = 0.52, 95% CI 0.41-0.66). Tislelizumab and nivolumab were associated with lower risks of grade ≥3 TRAEs. In etiology-stratified network analyses, atezolizumab plus bevacizumab (Atezo-Bev) showed the most consistent efficacy profile across virally mediated subgroups, with significant advantages for both OS and PFS in HBV-positive disease and a significant OS advantage in HCV-positive disease. However, no regimen achieved a statistically significant PFS advantage in the HCV-positive subgroup.ConclusionsFirst-line immunotherapy, compared to TKI monotherapy, provides meaningful survival benefits in advanced HCC, particularly in virally mediated disease, without significantly increasing severe toxicity. Among regimens, Sinti-Bev offers the most substantial OS advantage, while Anlo-Penpu and Camre-Rivo rank highest for PFS. Etiology-stratified analyses highlight Atezo-Bev as the most consistent regimen in virally mediated disease, with significant OS and PFS benefits in HBV-positive patients and a significant OS benefit in HCV-positive patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251131167, identifier CRD420251131167.